esam abdulkader el-hefian et al j.chem.soc.pak., …...esam abdulkader el-hefian et al.,...

Esam Abdulkader El-Hefian et al., J.Chem.Soc.Pak., Vol. 36, No. 1, 2014

11

Chitosan-Based Polymer Blends: Current Status and Applications

1 Esam Abdulkader El-Hefian*, 2 Mohamed Mahmoud Nasef and 3Abdul Hamid Yahaya 1Department of Chemistry, Faculty of Science, University of Zawia, Az Zāwīyah, Libya.

2Institute of Hydrogen Economy, Universiti Teknologi Malaysi, Jalan Semarak, 54100 Kuala Lumpur, Malaysia.

3Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. [email protected]*

(Received on 24th December 2012, accepted in revised form 8th November 2013)

Summary: This paper reviews the latest developments in chitosan-based blends and their potential applications in various fields. Various blends together with other derivatives, such as composites and graft copolymers, have been developed to overcome chitosan’s disadvantages, including poor mechanical properties and to improve its functionality towards specific applications. The progress made in blending chitosan with synthetic and natural polymers is presented. The versatility and unique characteristics, such as hydrophilicity, film-forming ability, biodegradability, biocompatibility, antibacterial activity and non-toxicity of chitosan has contributed to the successful development of various blends for medical, pharmaceutical, agricultural and environmental applications.

Keywords: review, chitosan, natural polymer, blend, application. Introduction

Natural polymers have attracted an increasing amount of attention over the last two decades, mainly due to their abundance, environmental concerns, and the anticipated depletion of petroleum resources. This has led to a growing interest in developing chemical and biochemical processes to obtain and modify natural polymers, and to utilise their useful inherent properties for a wide range of applications in different fields [1, 2].

Among the natural polymers, chitosan

occupies a special position due to its abundance, versatility, ease of modification and unique properties including biodegradability [3], biocompatibility [4, 5], non-toxicity [6] and anti-bacterial [7], as well as, hydrophilicity [8]. This has made chitosan a very useful compound in a broad range of applications in medical, pharmaceutical, chemical, agricultural and environmental fields.

To improve chitosan’s properties and further

diversify its applications, various strategies have been adopted. This includes: 1) crosslinking [9–11], 2) graft copolymerisation [12–16], 3) complexation [17–23], 4) chemical modifications [24, 25] and blending [26–29]. In particular, modification of chitosan by means of blending is an attractive method that has been extensively used for providing new desirable characteristics to chitosan [30–34]. This is mainly due to its simplicity, availability of a wide

range of synthetic and natural polymers for blending and effectiveness for practical utilisation.

Recently a number of review articles on

some derivatives (crosslinked, graft copolymers, complexes and composites), properties and potential applications of chitosan for pharmaceutical, veterinary medicine, biomedical and environmental fields have already been reported [35–45]. However, there is no specific review available on chitosan blends and their potential applications, despite the considerable amount of publications in this field.

This article reviews chitosan blends and

their various issues including methods of chitosan blending with synthetic and natural polymers. Moreover, applications of chitosan blends in the various fields ranging from biomedical to environmental applications are also presented with some focus on applications of growing interest. The scope of this review also covers basic fundamentals of chitosan including structure, preparation and applications. Chemical Structure and Preparation of Chitosan

Chitosan, 1→ 4 linked 2-amino-2-deoxy-β -D-glucopyranose, is the deacetylated derivative of chitin [46–49], the most abundant natural polymer (polysaccharide) on earth after cellulose [50-52]. The most important sources of chitin today are crustaceans [53-56], such as shrimps, squids and

*To whom all correspondence should be addressed.


12

crabs. Chitin and chitosan are similar to cellulose with respect to their physicochemical properties and their functions due to the similarity in molecular structure. Figure 1 shows the molecular structure of chitin, chitosan and cellulose. The only difference among the three polysaccharides is the acetamide group on the C-2 position of chitin and the amine group in chitosan instead of the hydroxyl group found in cellulose.

Fig. 1: Chemical structure of cellulose, chitin and

chitosan.

Chitin can be completely acetylated, completely deacetylated and partially deacetylated. In fact, complete deacetylation is rarely achieved. Chitosan is often described in terms of the average molecular weight and the degree of deacetylation (DD). In general, chitin with a degree of deacetylation of 70% or above is considered as chitosan [57]. Chitin and chitosan are both prepared using the common process illustrated and described in Figure 2 [58]. The raw chitosan is dissolved in aqueous 2% w/v acetic acid. Then, the insoluble material is filtered giving a clear supernatant solution, which is neutralised with NaOH solution resulting in a purified sample of chitosan as a white precipitate. Further purification may be necessary to prepare medical and pharmaceutical-grade chitosan.

Chitosan is commercially available. The

majority of its commercial samples are available with DD ranges between 70 to 90% and always less than 95% [59]. Tolaimate et al. [60] have reported that chitosan with DD higher than 95% may be obtained via further deacetylation steps. However, this may result in partial depolymerisation as well as increase the cost of the preparation. On the other hand, the DD can be lowered by reacetylation [46].

Fig. 2: Common process for preparation of chitin

and chitosan.

Properties of Chitin and Chitosan

Chitosan has become the subject of research due to its unique properties and ease of modification [61–63]. The physical [61], chemical [64] and

Decalcification in dil. Aqueous HCL solution (3–5% HCl w/v at room

temperature)

Deproteination in dil. aqueous NaOH solution (3–5% w/v NaOH, 80°C to

900°C for a few hrs. or at room temperature overnight)

Decolarization in 0.5% KMnO4 aqueous and oxalic acid aqueous or

sunshine

Deacetylation in hot conc. NaOH solution (40–50% w/v NaOH, at 90 °C

to 120°C for 4 to 5 hrs.

(shrimp, crab, lobster, krill, and squid)


13

biological properties [65, 66] of chitin and chitosan depend on two parameters: degree of deacetylation (DD) and molecular weight distribution [67], which are dictated by the chitin sources and the method of preparation [68]. In fact, the degree of deacetylation of chitosan influences not only its physicochemical characteristics, but also its biodegradability [69, 70]. In addition, the degree of deacetylation is also reported to have an impact on the performance of chitosan in many of its applications [71, 72]. Physical Properties

Chitosan exists in a form of white, yellowish flakes, which can be converted to bead or powders. The degree of deacetylation also plays a vital role on the molecular weight of chitosan. The lower the deacetylation, the higher the molecular weight, which provides higher chemical stability and mechanical strength. The average molecular weight of chitosan is approximately 1.2 × 105 g. mol-1 [73].

Chitin and chitosan are amorphous solids and almost insoluble in water. This is mostly due to intermolecular hydrogen bonding, which can form between the neutral molecules of chitosan. The solubility of chitosan in water depends upon the balance between the electrostatic repulsion resulting from the protonated amine functions and the hydrogen bonding due to the free amino groups [74].

Chitin is insoluble in most organic solvents.

It dissolves in corrosive chemicals such as N-dimethylacetamide (DMAC) containing lithium chloride. On the contrary, chitosan can be dissolved in aqueous organic acid solutions, such as formic acid and acetic acid at a pH below 6, and becomes a cationic polymer due to the protonation of the amino groups available in its molecular structure. However, chitosan hardly dissolves in pure acetic acid. In fact, concentrated acetic acid solutions at high temperatures may cause the depolymerisation of chitosan. The solubility of chitosan in dilute acids depends on the degree of deacetylation in the polymer chain. Consequently, this property can be used to distinguish between chitin and chitosan [75]. The degree of deacetylation is to be at least 85% complete so that the desired solubility of chitosan can be achieved. Furthermore, the properties of chitosan solutions depend not only on its average degree of deacetylation but also on the distribution of the acetyl groups along the chain [76, 77], the acid concentration and the type of acid [78].

Chitosan also dissolves in hydrochloric acid under certain conditions. However, it does not dissolve in sulfuric acid because of the formation of insoluble chitosan sulfate [79]. Aqueous solutions of some acids such as phosphoric, citric and sebacic acids are not good solvents [80]. Moreover, in the presence of a certain amount of acid, chitosan can be dissolved in some mixtures such as water/methanol and water/acetone. Chemical Properties

Similar to the most of natural polymers, chitosan has an amphiphilic character, which could influence its physical properties in solutions and solid states. This is attributed to the presence of the hydrophilic amino groups together with the hydrophobic acetyl groups in its molecular structure. The presence of large number of amino groups also confers chitosan a strong positive charge unlike most polysaccharides.

Chitosan has a cationic nature due to the presence of amino and hydroxyl groups, which make it modifiable by various means including complexation, grafting, crosslinking and blending [81]. Chitosan is a rigid polymer due to the presence of hydrogen bonding in its molecular structure. Consequently, it can be easily transformed into films with a high mechanical strength. Chitosan is a weak polyelectrolyte that may be regarded as a very poor anion-exchanger. Therefore, it is likely to form films on negatively charged surfaces in addition to the ability to chemically bind with negatively charged fats, cholesterol, proteins and macromolecules [57, 82]. Biological Properties

Chitosan is non-toxic, natural product [83, 84]. Therefore, it can be applied in the food industry for birds and fur-bearing animals. Moreover, chitosan is metabolised by certain human enzymes, especially lysozyme, and is considered as biodegradable [85, 86]. Chitosan is also biocompatible and, therefore, it can play a role in various medical applications such as topical ocular application [87], implantation [88] or injection [89]. Chitosan also has antibacterial, [90] wound-healing effects in humans [91] and animals [92–95] together with hemostatic activities [96]. It also has bioadhesive ability due to its positive charges at physiological pH [97]. A summary of the physical, chemical and biological properties of chitosan are listed in Table 1 [73, 98].


14

Table-1: Physical, chemical and biological properties of chitosan. Physical properties Chemical properties Biological properties

White yellow in colour Degree of acetylation range 70–95% Biocompatibility

Flakes, bead or powder Cationic polyamine Natural polymer High molecular weight

(1.2× 105 g mol-1) High charge density

at pHs < 6.5 Safe and non-toxic

Viscosity, high to low Forms gels with polyanions Haemostatic

Intermolecular hydrogen bonding

Linear weak polyelectrolyte

Biodegradable to normal body constituents

Amorphous solid Adheres to negatively charged surfaces

Bacteriostatic / Fungistatic

Density range 0.18 to 0.33 g cm-3

Chelates certain transitional metals Spermicidal

Soluble in diluted aqueous acid solution

e.g., acetic acid

Amiable to chemical modification Anticancerogen

Insoluble in water, alkali and organic

solvents

Reactive amino/hydroxyl

groups Anticholestermic

Applications of Chitosan

In the medical and pharmaceutical fields,

chitosan can be used for promoting weight loss [99]. This is due to its capability of binding a high amount of fats (about 4 to 5 times its weight) compared to other fibres. In addition, chitosan has no caloric value as it is not digestible, which is a significant property for any weight-loss product [100]. Therefore, it is used as a cholesterol-reducing agent [101]. Chitosan is also used as a wound-healing agent [102, 103, 94] in the form of a bandage [104], dressing burns [105], drug carriers [106–108], drug delivery system [109–111], preventing heart disease, controlling high blood pressure, preventing constipation, reducing blood levels of uric acid and producing artificial kidneys [112] due to the high mechanical strength of its membrane. In the eye-wear industry, chitosan has been used to produce contact lenses [113–115] more biocompatible than those made of synthetic plastic [105]. In cosmetics and personal care [116], it is used as face, hand and body creams. In addition, it can be applied for bath lotion and hair treatment due to its cationic charge, which makes it interact easily with negatively charged tissues like skin and hair [117].

In the chemical industry, chitosan is also

used in the paper industry as a thickener for printing and in coating paper because it is capable of interacting with fibers to form some bonds such as ionic, covalent and Van der Waals forces bonds which enhance paper stability and its resistance to outer influences [71]. In addition, owing to the smoother surface and resistance to moisture of the paper produced with chitosan, chitosan is used in the

production of toilet paper, wrapping paper and cardboard. In the photography field, chitosan is used for the rapid development of pictures.

In agriculture, chitosan is safely used for

controlled agrochemical release, seed coating [118]

and making fertilizer due to its biodegradability and natural origin. Recently, there has been some concern over its use in tissue engineering [57, 35,119].

In environmental applications, chitosan

plays an important role in wastewater treatment and industrial toxic pollution management [71,120] as it has the ability to adsorb dyes, pesticides, and toxic metals from water and wastewater. In addition, fibers of chitosan containing some enzymes are used in filters of gas masks as they detoxify harmful gases [121]. A summary of some applications of chitosan is shown in Table 2. More details on the various applications of chitosan can be found in recently published reviews [108, 122, 123]. Chitosan Blends

Polymer blending is a method that is

commonly used for providing desirable polymeric materials with combined properties for particular applications [30]. Recently, blends of natural polymers have been becoming considerably important due to their strong potential in replacing synthetic polymers in many applications [124] in addition of being renewable resources, nontoxic, inexpensive and leave biodegradable waste [125]. Among natural polymers, chitosan and its blends occupy a special position due to its versatility and suitability of a large number of applications as discussed earlier. Investigation of chitosan blends with synthetic and naturally occurring macromolecules has attracted much attention in recent years in various occasions [126–130].

Generally, there are two main methods that

are commonly used in the blending of chitosan: 1) dissolving in a solvent followed by evaporation (solution blending) [131, 132] and 2) mixing under fusion conditions (melt blending) [133]. However, according to the literature, solution blending is the most applied method for preparing chitosan blends due to its simplicity and suitability for producing various forms of blends (beads, microspheres, films and fibers).


15

Table-2: Some applications of chitosan. Application Examples Reference

Water treatment Filtration Removal of metal iron

[57] [57]

Medical

Bandages, Sponges Cholesterol reducing agent

Tumor inhibition Membranes

Dental plaque inhibition Skin burns/Artificial skin, Contact lens

Controlled release of drugs Bone disease treatment Wound healing agent

Drug carriers Dressing burns

Drug delivery system Producing artificial kidneys

[104] [101] [57] [57] [57] [57]

[113–115] [57] [57]

[102,103,94] [106–108]

[105] [109–111]

[112]

Cosmetics

Make-up powder Nail polish Moisturizer

Bath lotion and hair treatment Face, hand and body creams

Toothpaste

[57] [57] [57] [117] [116] [57]

Paper industry Surface treatment

Photographic paper Carbonless copy paper

[57] [57] [57]

Biotechnology

Enzyme immobilization Protein separation Glucose electrode Chromatography

[57] [57] [57] [57]

Agriculture Seed coating Hydrophonic/Fertilizer

[118] [57]

Food Removal of dyes, solids, acids Animal feed additives Color stabilization

[57] [57] [57]

Chemical industry Solvent separation Permeability control [57] [57]

In solution blending, chitosan is dissolved in

an appropriate solvent (usually diluted acetic acid) with continuous stirring at room temperature. This is followed by mixing a desired amount of another polymer after being dissolved in a solvent under continuous stirring conditions. The blend solution of chitosan is often crosslinked by addition of a crosslinking agent to improve mechanical properties. Subsequently, the blend solution is filtered and then cast on a glass plate or a petri dish and left to dry under room or oven temperature [134,135]. Eventually, the blend is washed with NaOH solution to remove the excess acetic acid. Table 2 presents a summary of the preparation of some chitosan blends using the casting method.

Like other polymer blends, the properties of

chitosan blends depends upon the miscibility of its components at the molecular scale, which is attributed to specific interactions between polymeric components. The most common interactions in the chitosan blends are: hydrogen bonding, ionic and dipole, π-electrons and charge-transfer complexes. Various techniques such as thermal analysis [136], electron microscopy [137], viscometric

measurements [138] and dynamic mechanical studies [139], have been used to investigate the polymer–polymer miscibility in solution or in solid state.

The purposes of chitosan blending vary

depending upon the application demands. This includes the following: 1) to enhance hydrophilicity [140, 141], 2) to enhance mechanical properties [142–146], 3) to improve blood compatibility [147–149] and 4) to enhance antibacterial properties [150]. In blood contact applications, chitosan promotes surface-induced thrombosis and embolization [147–149].

The selection of the polymers to be blended

with the chitosan depends on the property to be conferred or boosted. For example, the hydrophilic property of chitosan is modified by blending with polymers such as PEG and PVA [140, 141]. Chitosan was also blended with several polymers such as polyamides, poly (acrylic acid), gelatin, silk fibroin and cellulose to enhance mechanical properties [142–146]. To enhance antibacterial properties, chitosan is blended with cellulose 150.


16

Blends of chitosan with synthetic polymers Blending of chitosan with synthetic

polymers is a convenient method for preparation of synthetic biodegradable polymers having versatile properties, such as good water absorbance and enhanced mechanical properties (e.g., synthetic biodegradable polymers used as biomaterials range in tensile strength from 16 to 50 MPa and modulus from 400 to 3,000 MPa) while maintaining biodegradability [151]. Because of the large applications of chitosan in various fields, blends with synthetic polymers having wide range of physicochemical properties have been prepared in various occasions with solution blending investigated by many workers.

Polyvinyl alcohol and polyethylene are

among the synthetic polymers that have been frequently blended with chitosan [126, 127, 152, 153]. These blends represent new materials possessing better hydrophilicity, mechanical properties and biocompatibility than the characteristics of single components [154, 155]. The physico-chemical properties of chitosan/poly (vinyl alcohol) (PVA) blends using sorbitol and sucrose as plasticizers were investigated by Arvanitoyannis et al. [156]. Melting point and heat of fusion showed a decreasing trend with increasing the plasticizer content. However, the percentage of elongation together with CO2 and water vapor permeability of the blends showed an increase with increasing the plasticizer content coupled with a proportional decrease in the tensile strength and the modulus.

Graft copolymerization of chitosan with

acrylonitrile, methylmethacrylate (MMA), methacrylic acid, 2-hydroxyethylmethacrylate (HEMA), and acryl-amide has been reported in the literature. Similarly, styrene, vinyl acetate, acrylamide, MMA, and HEMA, have also been grafted on chitosan. Grafting of chitosan with N,N′-dimethylaminoethylmethacrylate (DMAEMA) has also been reported [131, 152, 157–159]. Blends of chitosan with polyurethane were prepared using a solvent casting method and their mechanical properties were evaluated [160]. Poor phase properties were reported.

Hybrid materials of chitosan with polynosic

(viscose rayon) were generated by a mechanical blending method. Chitin and chitosan were reacted with 1,6-diisocyanatohexane [poly-urea (urethanes)] in DMA-LiCl solutions and their properties evaluated [161].

Biodegradable films of chitosan blends containing polyethylene glycol (PEG) or polyvinyl alcohol (PVA) were prepared by mixing PEG or PVA with a solution of chitosan acetate, and films were prepared by the casting method [151, 148]. Homogenous films with increased values of initial temperature of thermal degradation were produced.

Chitosan-blended films containing glycerol

(0.25% and 0.5%) were prepared by Butler et al. [162]. Oxygen and ethylene permeability remained constant during the storage period, but percent elongation decreased.

Shieh and Huang [163] have reported the

preparation and characterization of chitosan/N-methylol nylon 6 blends in the form of membranes for the separation of ethanol-water mixtures by pervaporation. The obtained blend membranes were treated with H2SO4 to enhance their separation performance. The blend composition was found to play a significant role in affecting the performance of the membranes.

Wiles et al. [164] investigated the

mechanical properties of chitosan and polyethylene glycol (PEG) films. It was revealed that the obtained blend films containing PEG of 0.25% and 0.5% resulted in an increased percent of elongation, but tensile strength (TS) and water vapor transmission rate (WVTR) were decreased.

The mechanical properties of chitosan films

prepared by blending with polyols (glycerol, sorbitol and polyethylene glycol and fatty acids, stearic and palmitic acids) were studied by Srinivasa et al. [127]. Investigations of the mechanical properties showed a decrease in the tensile strength with the addition of polyols and fatty acids, while the percent of elongation was increased in polyol-blend films. However, fatty-blend films did not show any significant difference.

Attempts to prepare film blends of chitosan

with poly (lactic acid) (PLA) were reported by Nugraha et al. [165]. The thermal and mechanical properties of the obtained films revealed that chitosan/PLA blends are incompatible, i.e., there was no interaction between the two polymers.

Chitosan blends with polyvinyl pyrrolidone

(PVP) and polyethylene glycol (PEG) were reported by Zeng et al. [166]. The compatibility of the blends was proved by FTIR, wide angle x-ray diffraction (WAXD) and differential scanning calorimeter (DSC) analysis. The chitosan/PVP blend showed no


17

porosity unlike the chitosan/PEG blend, which showed high porosity. The former and latter are attributed to the strong and weak interactions in the blends, respectively.

Sandoval et al. [167] studied the

compatibility of two chitosan blends with (vinyl alcohol) (PVA) and poly(2-hydroxyethyl methacrylate) (P2HEM) through molecular dynamic simulations. The aim of this study was to find out which of the two functional groups (–CH2OH) and (–CH2OH), of chitosan is responsible for the interaction. It was concluded that the interaction occurs predominantly with the hydroxymethyl groups of chitosan at low composition of P2HEM and PVA, while the interaction with the amine groups increases with the increase in the composition of the two polymers.

Sarasam and Madihally [168] have reported

the preparation and characterization of chitosan/polycaproactone (PCA) blends at different ratios, temperatures, and humidities, for tissue engineering applications. According to the thermograms (using the Flory–Huggins theory), the two polymers were successfully blended. Measurements of differential scanning calorimetry (DSC) also indicated that there is an interaction between the two components when the results were analyzed using the Nishi–Wang equation. However, no remarkable alterations relative to chitosan were obtained by tensile properties measurements, while significant improvements were observed after solvent annealing. In addition, a significant improvement in mechanical properties was achieved when a 50:50 ratio blend dried at 55oC was used. It was concluded that such a blend has a potential for various applications in tissue engineering.

Chitosan was melt blended with poly- -

caprolactone (PCL), poly (butylene succinate) (PBS), poly (lactic acid) (PLA), poly (butylene terephthalate adipate) (PBTA), and poly (butylene succinate adipate) (PBSA) [133]. For the chitosan/PBS blend, the amount of chitosan varied from 25% to 70% by weight. The remaining polyesters had 50% of chitosan by weight. Addition of chitosan to PBS or PBSA tends to depress the melting temperature of the polyester. The crystallinity of the polyesters (PCL, PBS, PBSA) containing 50% chitosan decreased. Adding chitosan to the blends decreased the tensile strength but increased the tensile modulus. Chitosan displayed intermediate adhesion to the polyester matrix. Microscopic results indicated that the skin layer is polyester rich, while the core is a blend of chitosan and polyester. Fractured surface of chitosan

blended with a high Tg polymer, such as PLA, displayed a brittle fracture. Blends of chitosan with PCL, PBTA, or PBSA display fibrous appearances at the fractured surface due to the stretching of the polymer threads. Increasing the amount of chitosan in the blends also reduced the ductility of the fractured surface. The chitosan phase agglomerated into spherical domains was clustered into sheaths. Pull-out of chitosan particles is evident in tensile-fractured surfaces for blends of chitosan with ductile polymers but absent in the blends with PLA. PBS displays a less lamellar orientation when compared to PCL or PBSA. The orientation of the polyesters (PCL, PBSA) does not seem to be affected by the addition of chitosan.

Chitosan/nylon 11 blends at different ratios

were prepared and characterized by FTIR, scanning electron microscopy (SEM) and x-ray [169]. Biodegradability was also investigated. Results revealed that the physical properties of nylon 11 were greatly affected by the addition of chitosan in the blended films and that good biodegradability of the resulting blends was observed.

Smitha et al. [32] have reported the

preparation and characterization of the crosslinked blends of chitosan/nylon 66 at different weight compositions. The crosslinking and thermal stability of the blends after crosslinking were confirmed by FTIR and TGA, respectively. The obtained results showed good indication for dehydration of dioxane and moderate water sorption (50–90%) of the blends with no significant effects on mechanical stability of the blends. Increasing the water concentration in feed brought about an improved membrane swelling and, thereby, improved flux at reduced selectivity. Varying thickness resulted in a remarkable lowering of the flux with some improvement in selectivity. Higher permeate pressures caused a reduction in both the flux and selectivity.

Various proportions of three chitosan

portions having different molecular weights were blended with poly (N-vinyl-2-pyrrolidone) (PNV2P) [170]. The surface properties of the films were studied by scanning electron microscopy (SEM) and contact-angle measurements. It was revealed that the blend surfaces were enriched in low surface free energy component, i.e., chitosan.

Other studies on chitosan blends and

composites were reported in the literature. For example, chitosan/polyethylene glycol [171], chitosan/polyethylene oxide [172], chitosan/polyvinyl pyrrolidone [173],


18

chitosan/PVA/gelatin [174] and chitosan/PVA/pectin 175. Blends of chitosan with natural polymers

Blending of chitosan with other natural polymers has been proposed as an interesting method to bring about new bio-materials of improved properties to meet the requirements of specific applications. Reports on the blending of chitosan with natural polymers have been published in various occasions. For example, a number of publications have reported the blending of chitosan with collagen [128, 129, 176–178]. The effect of chitosan on the properties of collagen has also been investigated [30, 179, 180]. These studies have shown that chitosan has the ability to modify the mechanical properties of collagen.

Arvanitoyannis et al. [142] developed films

of chitosan and gelatin by casting from their combined aqueous solutions (pH 4.0) at 60°C and evaporating at 22 or 60°C (low- and high-temperature methods, respectively). The thermal, mechanical and gas/water permeation properties of these composite films, plasticized with water or polyols, were investigated. An increase in the total plasticizer content led to a considerable decrease of elasticity modulus and tensile strength, whereas the percentage of elongation increased. It was also found that the low-temperature preparation method led to a higher percentage of renaturation (crystallinity) of gelatin, therefore, a decrease, by 1–2 orders of magnitude, of CO2 and O2 permeability in the chitosan/gelatin blends was observed. An increase in the total plasticizer content (water or polyols) of these blends was found to be proportional to an increase in their gas permeability.

Ikejima et al. [26] reported the development

of blended films of microbial poly (3-hydroxybutyric acid) (PHB) with chitin and chitosan as completely biodegradable polyester/polysaccharide composites. DSC measurements revealed that crystallization of PHB in these blends was suppressed when the proportion of polysaccharides increased. The same tendency was evident from the FTIR band intensity of the carbonyl stretching absorption originated from PHB. Chitosan was found to have a stronger ability to suppress the crystallization of PHB than with chitin. PHB in the blends was found (by 13C NMR spectroscopy) to be trapped in the ‘glassy’ environment of the polysaccharide. Upon blending with PHB, the chitosan resonances were significantly broadened as compared to the chitin resonances. It was suggested that hydrogen bonds may be formed between the carbonyl groups of PHB and the amide -

NH groups of chitin and chitosan. The crystallization behavior and environmental biodegradability were also studied for the films of poly (3-hydroxybutyric acid) (PHB) blended with chitin and chitosan [27]. The blended films showed XRD peaks that arose from the PHB crystalline component. It was suggested that the lamellar thickness of the PHB crystalline component in the blends was large enough to show detectable XRD peaks. However, it was too small to show an observable melting endotherm in the DSC thermogram and a crystalline band absorption in the FTIR spectrum. The thermal transition temperatures of PHB amorphous regions observed by dynamic mechanical thermal analysis were almost the same as that of neat PHB for both PHB/chitin and PHB/chitosan blends. It was also observed that both blended films tend to biodegrade in an environmental medium.

Preparation of chitosan/κ-carrageenan

blends in the form of films has been studied. The effect of the type of solvent system (acetic, lactic, citric, maltic and ascorbic acids) on the mechanical properties on the obtained films was investigated [181]. Ascorbic acid was found to increase the tensile strength and the percent of elongation of the films compared to other diluting acids. Results showed that there are interactions among the organic acids and κ-carrageenan and chitosan.

Other kinds of aqueous blends based on

chitosan were also reported. Kweon et al. [182] reported the preparation of aqueous blends of chitosan with protein. Antheraea pernyi silk fibroin (SF)/chitosan-blended films were prepared by mixing an aqueous solution of A. pernyi SF and acetic acid solution of chitosan. The conformation of A. pernyi SF in the blended films was suggested to be a β-sheet structure, mainly due to the effect of using acetic acid as a mixing solvent. It was also found that the thermal decomposition stability of chitosan can be improved by blending with A. pernyi SF.

The phase structure of poly (R)-(3-

hydroxybutyrate) (PHB)/chitosan and poly (R)-(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(HB-co-HV))/chitosan blends using 1H CRAMPS (combined rotation and multiple pulse spectroscopy) was investigated by Cheung et al. [28]. A modified BR24 sequence that yielded an intensity decay to zero mode rather than the traditional inversion-recovery mode was used to measure 1H T1. Single exponential T1 decay is observed for the β-hydrogen of PHB or P (HB-co-HV) at 5.4 ppm and for the chitosan at 3.7 ppm. T1 values of the blends are either faster than or intermediate to those of the plain polymers. The


19

T1ρ decay of β-hydrogen is bi-exponential. The slow T1ρ decay component is interpreted in terms of the crystalline phase of PHB or P (HB-co-HV). The degree of crystallinity decreases with increasing wt% of chitosan in the blend. The fast T1ρ of β-hydrogen and the T1ρ of chitosan in the blends either follow the same trend as or are faster than the weight-averaged values based on the T1ρ of the plain polymers. Depending on the observation obtained by DSC of a melting point depression and one effective Tg in the blends, it was strongly suggested that chitosan is miscible with either PHB or P(HB-co-HV) at all compositions.

Lazaridou and Biliaderis [183] studied the

thermo-mechanical properties of aqueous solution/cast films of chitosan, starch/chitosan and pullulan/chitosan using dynamic mechanical thermal analysis (DMTA) and large deformation tensile testing. Incorporation of sorbitol (10% and 30% d.b.) and/or adsorption of moisture by the films resulted in substantial depression of the glass transition (Tg) of the polysaccharide matrix due to plasticization. The separate phase transitions of the individual polymeric constituents and the separate polyol phase for the composite films were not clear; a rather broad but single drop of elastic modulus, E′, and a single tan δ peak were observed. When the films were adjusted at various levels of moisture, the tensile test indicated large drops in Young's modulus and tensile strength (σmax) with increasing levels of polyol and moisture; the sensitivity of the films to plasticization was in the order of starch/chitosan>pullulan/chitosan>chitosan.

A series of chitosan/gelatin blend films has

been reported in various occasions 184. Good compatibility and an increase in the water uptake of chitosan films were observed. The chitosan/gelatin blend showed a higher percentage of elongation–at-break together with a lower Young’s modulus. In addition, the average water contact angles of the obtained films were found to be 60o. The investigation of chitosan/gelatin films for oxygen permeability, optical transmittance, water absorptivity and mechanical properties was also reported by Yuan and Wei [115]. The obtained results showed an increase in water absorption and improvement in oxygen and solute permeability of the composite film of chitosan. The chitosan/gelatin films were found to be more transparent, flexible and biocompatible.

Zhai et al. [185] reported the preparation of

antibacterial chitosan/starch-blended films. The chitosan/starch-blended films were prepared by irradiation of compression-molded, starch-based

mixtures in a physical gel state with an electron beam at room temperature. After the incorporation of 20% chitosan into the starch film, the tensile strength and the flexibility of the starch film were significantly improved. In addition, an interaction and microphase separation between the starch and chitosan molecules was observed by the X-ray diffraction (XRD) and SEM analyses of starch/chitosan-blended films. Moreover, the starch/chitosan-blended films were irradiated to produce a kind of antibacterial films. After irradiation, there was almost no change in the structure of the starch/chitosan-blended films. However, antibacterial activity was induced even when the content of chitosan was as low as 5%, due to the degradation of chitosan in the blended films under the action of irradiation.

Wu et al. [150] studied the preparation and

characterization of membranes of chitosan and cellulose blends using trifluoroacetic acid as a solvent. As far as the mechanical and dynamic mechanical thermal analyses are concerned, the cellulose/chitosan blends are almost incompatible. In addition, results obtained from water vapor transpiration rate and antibacterial measurements suggested the possibility of using the membranes of chitosan and cellulose as a wound dressing with antibacterial properties.

Suyatma et al. [29] reported the preparation

of biodegradable blend films of chitosan with polylactic acid by solution mixing and film casting. The incorporation of polylactic acid with chitosan improved the water barrier properties and decreased the water sensitivity of the chitosan films. However, the tensile strength and elastic modulus of chitosan decreased with the addition of polylactic acid. Measurements of mechanical and thermal properties revealed that chitosan and polylactic acid blends are incompatible. This was found to be consistent with the results of FTIR analysis that showed the absence of specific interactions between chitosan and polylactic acid.

Mucha and Pawiak [186] have reported that

films made from chitosan blends with hydroxylpropyl cellulose (HPC) resulted in good miscibility of components with better optical transparency and mechanical properties. The phase separation of the components occurred more drastically after water removal due to the active compatibilization behaviour of the water molecules in this system, which lead to the formation of additional hydrogen bonds.


20

Chitosan and starch blend films were prepared and characterized by Xu et al. [187]. The obtained films showed a decrease in the water vapor transmission rates and an increase in the tensile strength and the elongation-at-break with increasing starch ratio in the blend. FTIR spectroscopy and x-ray diffraction have suggested the existence of interactions and compatibility of the two film-forming components.

Wittaya-areekul and Prahsarn [188] have

investigated the possibility of incorporation of corn starch and dextran with chitosan using glutaraldehyde, a crosslinker used in wound dressing applications. The effect of adding polypropylene glycol (as a plasticizer) on the chitosan blends was also reported. Results showed that corn starch and dextran can be incorporated into chitosan film to improve the physical strength, i.e., vapor penetration, water uptake, and oxygen penetration properties. The addition of propylene glycol was found to improve the film elasticity and all other properties mentioned already with the exception of bio-adhesive properties.

Yin et al. [189] have examined the miscibility of chitosan blends with two cellulose ethers, hydroxypropylmethylcellulose and methylcellulose by infrared spectroscopy, thermal gravimetric analysis, wide-angle X-ray diffraction and scanning electron microscopy. It was concluded that full miscibility cannot be achieved if the hydrogen bonding between the polymers is weak.

The miscibility of chitosan/gelatin blends in

a buffer solution (0.2 M sodium acetate and 0.1 N acetic acid) has been assessed by means of viscosity, ultrasonic and refractive index methods at 30 and 50oC [190]. The obtained data indicated that the blend is immiscible in all proportions, and that the variation of temperature has no influence on miscibility of the blend.

The compatibility of chitosan/collagen

blends has been evaluated by dilute solution viscometry [191]. The obtained data showed that collagen/chitosan blends are miscible at any ratio in acetic acid solutions at 25oC. As far as the “memory effect’’ is concerned, the blends are also miscible in the solid state.

Elhefian et al. [192] reported the preparation

and characterization of chitosan/agar-blended films. The FTIR results and thermal analysis showed that

the interactions (intermolecular hydrogen bonding) among the functional groups of the blend components can occur.

A summary of some chitosan blends with

synthetic and natural polymers including their preparation by the casting technique suggested by some authors is presented in Table 3.

Some Applications of Chitosan Blends

According to the literature, most of the applications of chitosan blends are in the pharmaceutical and biomedical fields. For example, chitosan has been receiving increasing interest in drug delivery applications due to its capacity to enhance the transport of hydrophilic drugs. It has also reported to be useful in colon- or nasal delivery. Chitosan is also of current interest as a carrier in gene delivery. Several chitosan nanocomposites were evaluated based on the ionotropic gelation, or numerous chitosan/DNA nanoparticles were framed from the complexation of the cationic polymer with DNA plasmids. Ionically interaction and modification only of chitosan as cationic polymers and anions result in these particles.

In the area of drug delivery systems, chitosan blends have been widely used for control release of drugs because of their advantageous properties, such as non-toxicity, biocompatibility, biodegradability and availability of terminal functional groups [197]. Various physical forms of chitosan blends, such as microparticles [198], tablets [199], films [200], beads [201], gels [202] were proposed for various drug release applications and as an absorption enhancer for nasal and oral drug delivery [203]. For example, various blends of collagen and chitosan were used for the architecture of membranes for controlled release [176, 177, 204]. This also included proposing chitosan as a useful excipient for obtaining sustained release of water-soluble drugs and for enhancing the bioavailability of poorly water-soluble compounds. Moreover, chitosan has also been presented as a useful polymer for colon-specific and oral administered drug delivery [205]. This has derived huge research efforts that led to the publication of an immense number of studies for a wide variety of applications in the field of controlled release (over 2,000 papers in the last 15 years), which makes it impossible to be reviewed here.

Table-3: A summary of some chitosan blends with synthetic and natural polymers including their preparation by the casting technique suggested by some authors. Chitosan source /(DD) Solvent used Blend Crosslinker Plasticizer Film Ref.


21

thickness

Shrimp/85%

1%(v/v) acetic acid

CS/glycerol CS/sorbitol

CS/PEG CS/tween60 CS/tween 80

_

_

2.82–3.95× 10-2

[193]

91% 1%(w/v) acetic acid CS/gelatin _ _ _ [115] 2.0 wt% acetic acid CS/cellulose _ _ _ [150]

Crab/80-85% 1% acetic acid CS/PLA _ _ _ [29]

Shrimp/80% 2% acetic acid PA/CS Glutaraldehyde _ _ [194]

Crab/> 85% 1% acetic acid CS/gelatin _ _ _ [184]

56% 5% acetic acid+1% HCl

(catalyzer)

HPC/CS Glyoxal and

glutaraldehyde

_ 20-30µm [153]

96% Lactic acid CS/cornstarch

Glutaraldehyde Propylene (8)

Lactic acid CS/cornstarch CS/dextran

glutaraldehyde

Propylene glycol (PG)

_ [188]

60%

(0.2 M sodium CS/gelatin (9) acetate + 0.1 N

acetic acid)

CS/gelatin _

_

_ [190]

95.7% 1% acetic acid CS/CE _ _ _ [189] 90%

1% (v/v) lactic acid CS/starch _ Glycerin ~ 2.54 µm [187]

_ 2% acetic acid CS/PVA _ Sorbitol and sucrose _ [156]

91% 2% acetic acid CS/PVP CS/PEG _ _ 40–60 µm [166]

85% 0.5M acetic acid CS/ collagen _ _ _ [191]

~ 84% trifluoroacetic

acid (TFA)

CS/nylon 11 _ _ _ [169]

85, 87 and 93% 4 wt% acetic acid (PNV2P)/CS _ _ 40–50 µm [170]

84% Formic acid CS/ nylon 66

sulfuric acid _ _ [32]

~ 85% o.5M acetic acid CS/ PCA _

_

50–60 µm (dry) and

90–120 µm (wet)

[168]

- 88 wt% formic acid CS/ NMN6 1M H2SO4 20–40 µm [163]

80% 0.5% (v/v) acetic acid CS and poly (sodium-4-styrene sulphonate) - - - [195]

75–85% 2% acetic acid CS/PVA - - - [196]

The tissues engineering field is another biomedical field where chitosan blends and other forms have found growing interest. Chitosan-based materials have been reported for tissue engineering in different physical forms, including porous scaffolds and gels [35, 206–208]. For example, blends of collagen and chitosan have been used for the design of polymeric scaffolds for the in vitro culture of human cells, tissue engineering skin and implant fibers [128, 209].

As an anti-microbial agent, chitosan is a biopolymer that has been well known as being able to accelerate the healing of wounds in humans [210]. It was reported that chitosan stimulated the migration of polymorphonuclear (PMN) as well as mononuclear cells and accelerated the re-epithelialization and

normal skin regeneration [211]. The antimicrobial activity of chitosan is well known against a variety of bacteria and fungi coming from its polycationic nature [212]. The interaction between positively charged chitosan and negatively charged microbial cell walls leads to the leakage of intracellular constituents. The binding of chitosan with DNA and inhibition of mRNA synthesis occur via the penetration of chitosan into the nuclei of the microorganisms and interfering with the synthesis of mRNA and proteins. Furthermore, chitosan is a biomaterial widely used for effective delivery of many pharmaceuticals [213]. Accordingly, chitosan may be suitable for incorporating other antipyrotics for the preparation of long-acting antibacterial wound dressings.


22

In environmental applications, due to its powerful chelating ability, chitosan was found to be among the most powerful heavy metal ion binders [214]. This is performed mainly with the use of chitosan-based powders, flakes, gel beads, composite membranes or others [215–217]. In general, the affinity of chitosan to heavy metal ions is as follows: Pd>Au>Hg>Pt>Cu>Ni>Zn>Mn>Pb>Co>Cr>Cd>Ag [75, 218, 219]. Chitosan blends can be also applied for the dehydration of solvents. For instance, it has been reported that chitosan/N-methylol nylon 6 blend membranes can be used for the separation of ethanol-water mixtures in terms of acid (H2SO4) post-treatment, feed concentration, blend ratio and temperature [163]. Recently, some chitosan-blended films have been developed for food packaging applications [220–222]. This is mainly due to their antimicrobial activity, good water resistance, biodegradability, good thermal properties, biocompatibility and non-toxicity.

Conclusion

Chitosan is a natural polymer that has proposed for a wide variety of applications ranging from food packaging to a drug carrier. In this review, an attempt has been made for better understanding of chitosan and its blends in various aspects. This includes its physical, chemical and biological properties as well as the preparation and characterization of its blends with other materials and their applications.

Acknowledgement

The authors wish to acknowledge the financial support for this research project from University of Malaya under the research grant No PS188/2008A

LIST OF ABBREVIATIONS

The following abbreviations have been used in the text: CS Chitosan DD Degree of deacetylation PA Polyaniline PVA Poly vinyl alcohol PEG Polyethylene glycol PLA Poly lactic acid PVP Polyvinyl pyrrolidone HPC Hydroxyl propyl cellulose P2HEM Poly (2-hydroxyethyl methacrylate) PNV2P Poly (N-vinyl-2- pyrrolidone) NMN6 N-methylol nylon 6 PCA Poly caprolactone PG Propylene glycol CE Cellulose ethers

References 1. L IIIum, Pharmaceutical Research, 15, 1326

(1998). 2. J Akbuga, International Journal of

Pharmaceutics Advances, 1, 1 (1995). 3. Y M Dong, B W Qiu, H Y Ruan, S Y Wu, M A

Wang and C Y Xu, Polymer Journal, 33, 387 (2001).

4. Y Shigemasa and S Minami, Biotechnology and Genetic Engineering Reviews, 13, 383 (1995).

5. G. Borchard and H E Junginger, Advanced Drug Delivery Reviews, 52, 103 (2001).

6. J Karlsen and O Skaugrud, Manufacturing Chemist., 62, 18 (1991).

7. G. F Payne, W Q Sun and A Sohrabi, Biotechnology and Bioengineering, 40, 1011 (1992).

8. A Niekraszewicz, H Struszczyk, M Kucharska, Advances in Chitin Science, 2, 678 (1997).

9. A. S. Aly, Angewandte Makromolekulare Chemie, 259, 13 (1998).

10. E. B. Denkbas, M. Seyyal and E Piskin, Journal of Membrane Science, 172, 33 (2000).

11. K Yamada, T Chen, G Kumar, O Vesnovsky, L D Timmie and G F Payne, Biomacromolecules., 1, 253 (2000).

12. M Yazdani-Pedram, J Retuert and R Quijada, Macromolecular Chemistry and Physics, 201, 923 (2000).

13. A Borzacchiello, L Ambrosio, P A Netti, L Nicolais, C Peniche, A Gallardo, et al, Journal of Materials Science Materials in Medicine, 12, 861 (2001).

14. D W Jenkins and S M Hudson, Macromolecules, 35, 3413 (2002).

15. G. R. Mahdavinia, A Pourjavadi, H Hosseinzadeh and M J Zohuriaan, European Polymer Journal, 40, 1399 (2004).

16. G Huacai, P Wan and L Dengke, Carbohydrate Polymers, 66, 372 (2006).

17. T. Sun, P. X. Xu, Q Liu, J. A. Xue and W. M Xie, European Polymer Journal, 39, 189 (2003).

18. W. M. Xie, P. X. Xu, Q Liu and J Xue, Polymer Bulletin, 49, 47 (2002).

19. T. M Don, C F King and W Y Chiu, Journal of Applied Polymer Science, 86, 3057 (2002).

20. S. Y. Kim, S. M. Cho, Y. M Lee and S J. Kim, Journal of Applied Polymer Science, 78, 1381 (2000).

21. M. Y. Pedram and J. Retuert, Journal of Applied Polymer Science, 63, 1321 (1997).

22. M. Y Pedram, J. Retuert and R. Quijada, Macromolecular Chemistry and Physics, 201, 923 (2000).


23

23. H. S Blair, J. Guthrie, T. K. Law and P. Turkington, Journal of Applied Polymer Science, 33, 641 (1987).

24. L D Hall and M Yalpani, Journal of the Chemical Society, Chemical Communications, 23, 1153 (1980).

25. M. Yalpani and L. D Hall, Macromolecules, 17, 272 (1984).

26. T. Ikejima, K Yagi and Y Inoue, Macromolecular Chemistry and Physics, 200, 413 (1999).

27. T. Ikejima and Y Inoue, Carbohydrate Polymers, 41, 351 (2000).

28. M. K. Cheung, K. P. Y. Wan and P. H. Yu, Journal of Applied Polymer Science, 86, 1253 (2002).

29. N. E. Suyatma, A. Copinet, L. Tighzert and V. Coma, Journal of Polymers and the Environment, 12, 1 (2004).

30. M. N. Taravel and A. Domard, Biomaterials, 17, 451 (1996).

31. B. Smitha, S. Sridhar and A. A Khan, Journal of Membrane Science, 225, 63 (2003).

32. B. Smitha, G. Dhanuja and S. Sridhar, Carbohydrate Polymers, 66, 463 (2006).

33. A. Chanachai, R. Jiraratananon, D. Uttapap, G. Y. Moon, W. A. Anderson and R. Y. M. Huang, Journal of Membrane Science, 166, 271 (2000).

34. L. Ma, C. Y. Gao, Z. W. Mao, J. Zhou, J. C. Shen, X. Q. Hu and C. M. Han, Biomaterials, 24, 4833 (2003).

35. J. K. F. Suh and H. W. T. Matthew, Biomaterials, 21, 2589 (2000).

36. M. N. V. Ravi Kumar, Reactive and Functional Polymers, 46, 1 (2000).

37. M. N. V. Ravi Kumar, R. A. A. Muzzarelli, C Muzzarelli, H. Shashiwa and A. J. Domb, Chemical Reviews, 104, 6017 (2004).

38. J. Berger, M. Reist, J. M. Mayer, O. Belt and R. Gurny, European Journal of Pharmaceutics and Biopharmaceutics, 57, 35 (2004).

39. S. Senel and S. J McClure, Advanced Drug Delivery Reviews, 56, 1467 (2004).

40. A. J. Varma, S. V. Deshpande and J. F. Kennedy, Carbohydrate Polymers, 55, 77 (2004).

41. E. Guibal, Separation and Purification Technology, 38, 43 (2004).

42. M. Prabaharan and J. K. Mano, Carbohydrate Polymers, 63, 153 (2006).

43. R. Jayakumar, M. Prabaharan, R. L. Reis and J. F. Mano, Carbohydrate Polymers, 62, 142 (2005).

44. A. Domard, Carbohydrate Polymers, 84, 696 (2011).

45. C. Gerente, V. K. Lee, L. E. Cloirec and G. McKay, Critical Reviews in Environment Science and Technology, 37, 41 (2007).

46. R. A. A. Muzzarelli, Natural Chelating Polymers; Pergamon Press Ltd: Oxford, p. 144 (1973).

47. H. I. Bolker, Natural and Synthetic Polymer: an introduction; Marcel DekkerInc: New York, p. 106 (1974).

48. J. D. Dee, O. Rhode and R. Wachter, Cosmetics and Toiletries, 116, 39 (2001).

49. A. K. Singla and M. Chawla, Journal of Pharmacy and Pharmacology, 53, 1047 (2001).

50. H. K. No and S. P. Meyers, Journal of Agricultural and Food Chemistry, 37, 580 (1989).

51. K. Kurita, Polymer Degradation and Stability, 59, 117 (1998).

52. S. E. Bailey, T. J. Olin, R. M. Bricka and D. D. Adrian, Water Research, 33, 2469 (1999).

53. Y. Sawayanagi, N. Nambu and T. Nagai, Chemistry and Pharmacology Bulletin, 31, 2064 (1983).

54. T. C. Yang and R. R. Zull, Industrial And Engineering Chemistry Product Research And Development, 23, 168 (1984).

55. J. Yanga, I. I. Shih, Y. Tzengc and S. Wang, Enzyme and Microbial Technology, 26, 406 (2000).

56. T. A. Khan, K. K. Peh and H. S. Ch’ng, Journal of Pharmaceutical Sciences, 5, 205 (2002).

57. Q. Li, E. T. Dunn, E. W. Grandmaison and M. F Goosen, Journal of Bioactive and Bompatible Polymer, 7, 370 (1992).

58. P. A. Sanford, Chitosan: Commercial uses and potential applications, in G Skjak, T Anthonsen, P Sanford (Eds), Chitin and Chitosan - sources, Chemistry, Biochemistry, Physical Properties and Applications; Elsevier: London, UK, p. 51 (1989).

59. E. Guibal, Separation and Purification Technology, 38, 43 (2004).

60. A. Tolaimate, J. Desbrieres, M. Rhazi and A. Alagui, Polymer, 44, 7939 (2003).

61. S. Mima, M. Miya, R. Iwamoto, S. Yoshikawa, Journal of Applied Polymer Science, 28, 1909 (1983).

62. T. Seo, H. Ohtake, T. Kanbara, K. Yonetake and T. Iijima, Die Makromolekulare Chemie, 192, 2461 (1991).

63. M. Mucha, Macromolecular Chemistry and Physics, 198, 471 (1997).

64. H. Miyoshi, K. Shimahara, K. Watanabe and K. Onodera, Bioscience Biotechnology and Biochemistry, 56, 1901 (1992).


24

65. K. Nishimura, S. Nishimura, N. Nishi, I. Saiki, S. Tokura and I. Azuma, Vaccine, 2, 93 (1984).

66. K. Nishimura, S. Nishimura, N. Nishi, F. Numata, Y. Tone, S. Tokura and I. Azuma, Vaccine, 3, 379 (1985).

67. E. I. Rabea, M. E. T. Badawy, C. V. Stevens, G. Smagghe and W. Steurbaut, Biomacromolecules, 4, 1457 (2003).

68. C. J. Brine and P. R. Austin, Comparative Biochemistry and Physiology, 69B, 283 (1981).

69. N. Hutadilok, T. Mochimasu, H. Hisamori, K. Hayashi, H. Tachibana, S. Ishii and H. Hirano, Carbohydrate Research, 268, 143 (1995).

70. R. J. Nordtveit, K. M. Varum and O. Smidsrod, Carbohydrate Polymers, 29, 163 (1996).

71. R. A. A. Muzzarelli, Chitin; Pergamon Press Ltd: Hungary, p. 83 (1977).

72. S. E. Lower, Manufacturing Chemist, 55, 73 (1984).

73. K. Nagasawa, Y. Tohira, Y. Inoue and N. Tanoura, Carbohydrate Research, 18, 95 (1971).

74. A. Domard, Physico-Chemical and Structural basis for Applicability of Chitin and Chitosan. The proceedings of the Second Asia Pacific Symposium of chitin and chitosan. Bangkok, Thailand, p. 1 (1996).

75. M. G. Peter, Journal of Macromolecular Science Pure and Applied Chemistry, 32, 629 (1995).

76. S. Aiba, International Journal of Biological Macromolecules. 13, 40 (1991).

77. N. Kubota and Y. Eguchi, Polymer Journal, 29, 123 (1997).

78. K. Kurita, Progress in Polymer Science, 26, 1921 (2001).

79. R. Yamaguchi, S. Hirano, Y. Arai and T. Ito, Agricultural and Biological Chemistry, 42, 1981 (1978).

80. P. Gross, E. Konrad and H. Mager, Sonderdr Parfum Kosmet, 64, 367 (1983).

81. A. Denuziere, D. Ferrier, O. Damour and A. Domard, Biomaterials, 19, 1275 (1998).

82. P. A. Sandford, Front. Carbohydrate Research, 2, 250 (1992).

83. K. Arai, T. Kinumaki and T. Fugita, Bulletin of Tokai Regional Fisheries Research Laboratory, 56, 89 (1968).

84. S. Hirano, H. Sino, Y. Akiyama and I. Nonaka, Polymeric Materials Science and Engineering, 59, 897 (1988).

85. R A. A. Muzzarelli, Cellular and Molecular Life Sciences, 53, 131 (1997).

86. D. Koga, Chitin Enzymology Chitinase, in: R. Chen and H. C Chen (Eds), Advances in Chitin Science, p. 16 (1998).

87. O. Felt, P. Furrer, J. M. Mayer, B. Plazonnet, P. Buri and R. Gurny, International Journal of Pharmaceutics, 180, 185 (1999).

88. S. Patashnik, L. Rabinovich and G. Golomb, Journal of Drug Targeting, 4, 371 (1997).

89. J. S. Song, C. H. Such, Y. B. Park, S. H. Lee, N. C. Yoo, J. D. Lee, K. H. Kim and S. K. Lee. European Journal of Nuclear Medicine, 28, 489 (2001).

90. X. F. Liu, Y. L. Guan, D. Z. Yang, Z. Li and K. D. Yao, Journal of Applied Polymer Science, 79, 1324 (2001).

91. H. Ueno, T. Mori and T. Fujinaga, Advanced Drug Delivery Reviews, 52, 105 (2001).

92. R. A. A. Muzzarelli, V. Baldassarre, F. Conti, G. Gazzanelli, V. Vasi, P. Ferrara and G. Biagini, Biomaterials, 9, 247 (1988)

93. Y. Okamoto, S. Minami S. Matsuhashi, H. Sashiwa, H. Saimoto, Y. Shigemasa, T. Tanigawa, Y. Tanaka and S. Tokura, Application of chitin and chitosan in small animals, in: Brine C J, Sandford P A and Zikakis J P (Eds), Advances in Chitin and Chitosan, London: Elsevier, p. 70 (1992).

94. H. Ueno, H. Yamada, I. Tanaka, N. Kaba, M. Matsuura, M. Okumura, T. Kadosawa and T. Fujinaga, Biomaterials, 20, 1407 (1999).

95. K. Mizuno, K. Yamamura, K. Yano, T. Osada, S. Saeki, N. Takimoto, T. Sakura and Y. Nimura, Journal of Biomedical Materials Research, 64, 177 (2003).

96. W. G. Malette, H. J. Quigley, R. D. Gaines, N. D. Johnson and W. G. Rainer, The Annals of Thoracic Surgery, 36, 55 (1983).

97. P. He, S. S. Davis and L. Illum, International Journal of Pharmaceutics, 166, 75 (1998).

98. P. A. Sanford, Chitosan: Commercial uses and potential applications, in: G Skjak, T Anthonsen, P Sanford (Eds), Chitin and chitosan - sources, chemistry, biochemistry, physical properties and applications, Elsevier, London, UK, p. 51 (1989).

99. D. V. Luyen and V. Rossbach, Technical Textiles, 35, 19 (1992).

100. O. Kanauchi, K. Deuchi, Y. Imasato, M. Shizukuishi and E. Kobayashi, Bioscience Biotechnology and Biochemistry, 59, 786 (1995).

101. D. T. Gordon, Action of amino acids on iron status, gut morphology, and cholesterol levels in the rat, in, J P Zikakis (Eds), Chitin, chitosan and related enzymes, New York, Academic Press, p. 97 (1984).

102. L. L. Lioyd, J. F. Kennedy, P. Methacanon, M. Paterson and C. J. Knill, Carbohydrate Polymers, 37, 315 (1998).


25

103. Y. W. Cho, Y. N Cho, S H Chung and W Ko, Biomaterials, 20, 2139 (1999).

104. K. Sathirakul, N. C. How, W. F. Stevens and S. Chandrkrachang, Advances in Chitin Science, 1, 490 (1996).

105. G. G. Allan, L. C. Altman, R. E. Bensinger, D. K. Ghosh, Y. Hirabayashi, A. N. Neogi and S. Neogi, Biomedical applications of chitin and chitosan, in: chitin, chitosan and related enzymes, J P Zikakis (Eds), Academic Press, New York, p. 119 (1984).

106. O. Pillai and R. Panchagnula, Current Opinion in Chemical Biology, 5, 447 (2001).

107. R. Hejazi and M. M. Amiji, Journal of Controlled Release, 89, 151 (2003).

108. E. Khor and L. Y. Lim, Biomaterials, 24, 2339 (2003).

109. Y. Sawayanagi, N. Nambu and T. Nagai, Chemical and Pharmaceutical Bulletin, 30, 4213 (1982).

110. S. B. Park, J. O. You, H. Y. Park, S. J. Haam and W. S. Kim, Biomaterials, 22, 323 (2001).

111. J. Nunthanid, M. Laungtana-anan, P. Sriamornsak, S. Limmatvapirat, S. Puttipipatkhachorn, L. Y. Lim and E. Khor, Journal of Controlled Release, 99, 15 (2004).

112. S. Hirano and Y. J. Noishiki, Journal of Biomedial Materials Research, 19, 413 (1985).

113. M. L. Markey, L. M. Browman and M. V. W. Bergamini, Contact lenses made from chitosan. Chitin and chitosan. Proceedings of the 4th International Conference on chitin and chitosan.Trondheim, Norway, p. 713 (1988).

114. R. Olsen, D. Schwartzmiller, W. Weppner and R. Winandy, Biomedical applications of chitin and its derivatives, chitin and chitosan; Elsevier Applied Science: London, New York, p. 813 (1989).

115. S. Yuan and T. Wei, Journal of Bioactive and Compatible Polymers, 19, 467 (2004).

116. P. Gross, E. Konrad and H. Mager, Sonderdr Parfum Kosmet, 64, 367 (1983).

117. U. Griesbach, C. Panzer and R. Wachter, Cosmetics and Toiletries, 114, 81 (1999).

118. R. L. Rawls, Chemical and Engineering News, 62, 42 (1984).

119. M. V. Risbud, K. E. Karamuk, R. Moser and J. Mayer, Cell Transplantation, 11, 369 (2002).

120. G. Crini, Bioresource Technology, 97, 1061 (2006).

121. L. Ember, Detoxifying Nerve Agents: Academic, Army, and Scientists Join Forces on Enzyme Anchored in Foams and Fiber, Chemical and Engineering News, September 15, p. 26 (1997).

122. N. V. Majeti and R. Kumar, Reactive and Functional Polymers, 46, 1 (2000).

123. M. Rinaudo, Progress in Polymer Science, 31, 603 (2006).

124. D. Wood, European patents for biotechnological inventions-past, present and future. World Patent Information, 23, p. 339 (2001).

125. C. G. T. Neto, J. A. Giacometti, A. E. Job, F. C. Ferreira, J. L. C. Fonseca and M. R. Pereira, Carbohydrate Polymers, 62, 97 (2005).

126. M. Mucha, Reactive and Functional Polymers, 38, 19 (1998).

127. P. C. Srinivasa, M. N. Ramesh, K. R. Kumar and R. N. Tharanathan, Carbohydrate Polymers, 2003, 53, 431 (2003).

128. N. Shanmugasundaram, P. Ravichandran, P. R. Neelakanta, R. Nalini, P. Subrata and K. P. Rao, Biomaterials, 22, 1943 (2001).

129. X. G. Chen, Z. Wang, W. S. Liu and H. J. Park, Biomaterials, 23, 4609 (2002).

130. A. Sionkowska, M. Wisniewski, J. Skopinska, C. J. Kennedy and T. J. Wess, Biomaterials, 25, 795 (2004).

131. D. K. Singh, A. R. Ray, Journal of Applied Polymer Science, 66, 869 (1997).

132. S. Yoshikawa, T. Takeshi and N. Tsubokawa, Journal of Applied Polymer Science, 68, 1883 (1998).

133. V. M. Correlo, L. F. Boesel, M. Bhattacharya, J. F. Mano, N. M. Neves and R. L. Reis, Materials Science and Engineering A, 403, 57 (2005).

134. N. F. Mohd Nasir, N. Mohd Zain, M. G. Raha and N. A. Kadri, American Journal of Applied Sciences, 2 , 1578 (2005).

135. Q. I, Q. Li, J. Wei Lu, Z. Xia and J. Yu, Chinese Journal of Polymer Science, 27, 387 (2009).

136. J. C. Cabanelas, B. Serrano, J. Baselga, Macromolecules, 38, 961 (2005).

137. O. Olabisi, L. M. Robeson and M. T. Shaw, Polymer–polymer miscibility. Academic press, New York, p. 164 (1979).

138. W. H. Jiang and S. Han, European Polymer Journal, 34, 1579 (1998).

139. K. Lewandowska, European Polymer Journal, 41, 55 (2005).

140. D. K. Kweon and D. W. Kang, Journal of Applied Polymer Science, 74, 458 (1999).

141. M. Zhang, X. H. Li, Y. D. Gong, N. M. Zhao and X. F. Zhang, Biomaterials, 23, 2641 (2002).

142. I. Arvanitoyannis, I. Nakayama and S. Aiba, Carbohydrate Polymers, 37, 371 (1998).

143. A. Isogai and R. H Atalla, Carbohydrate Polymers, 19, 25 (1992).

144. J. W. Lee, S. Y. Kim, S. S. Kim, Y. M. Lee, K. H. Lee and S. J. Kim, Journal of Applied Polymer Science, 73, 113 (1999).


26

145. S. R. Park, K. Y. Lee, W. S. Ha and S. Y. Park, Journal of Applied Polymer Science, 74, 2571 (1999).

146. J. A. Ratto, C. C. Chen and R. B. Blumstein, Journal of Applied Polymer Science, 59, 1451 (1996).

147. M. M. Amiji, Carbohydrate Polymers, 26, 211 (1995).

148. T. Chandy and C. P. Sharma, Journal of Applied Polymer Science, 44, 2145 (1992).

149. M. Ishihara, K. Nakanishi, K. Ono, M. Sato, M. Kikuchi, Y. Saito, H. Yura, T. Matsui, H. Hattori, M. Uenoyama and A. Kurita, Biomaterials, 23, 833 (2002).

150. Y. B. Wu, S. H. Yu, F. L. Mi, C. W. Wu, S. S. Shyu, C. K. Peng et al, Carbohydrate Polymers, 57, 435 (2004).

151. I. Engelberg and J. Kohn, Biomaterials, 12, 292 (1991).

152. H. S. Blair, J. Guthrie, T. K. Law and P. Turkington, Journal of Applied Polymer Science, 33, 641 (1987).

153. S. Suto and N. Ui, Journal of Applied Polymer Science, 61, 2273 (1996).

154. M. G. Cascone, Polymer International, 43, 55 (1997).

155. C. Xiao, Y. Lu, H. Liu and L. Zhang, Journal of Macromolecular Science Pure and Applied Chemistry, 37, 1663 (2000).

156. I. Arvanitoyannis, I. Kolokuris, A. Nakayama, N. Yamamoto and S. Aiba, Carbohydrate Polymers, 34, 9 (1997).

157. D. K. Singh and A. R. Ray, Journal of Applied Polymer Science, 53, 1115 (1994).

158. A. Lagos and J. Reyes, Journal of Polymer Science Part A: Polymer Chemistry, 26, 985 (1988).

159. Y. Shigeno, K. Kondo and K. Takemoto, Journal of Macromolecular Science-Chemistry, A 17, 571 (1982).

160. P. Gong, L. Zhang, L. Zhuang and J. Lu, Journal of Applied Polymer Science, 68, 1321 (1998).

161. R. A. A. Muzzarelli, P. Ilari and M. B. Tomasetti, Journal of Biomaterials Science Polymer Edition, 6, 541 (1994).

162. B. L. Butler, P. J. Vergano, R. F. Testin, J. M. Bunn and J. L. Wiles, Journal of Food Science, 61, 953 (1996).

163. J. J. Shieh and R. Y. M. Huang, Journal of Membrane Science, 148, 243 (1998).

164. J. L. Wiles, P. J. Vergano, F H Barron, J M Bunn and R. F. Testin, Journal of Food Science, 65, 1175 (2000).

165. E. S. Nugraha, A. Copinet, L. Tighzert and V. Coma, Journal of Polymers and the Environment, 12, 1 (2004).

166. M. Zeng, Z. Fang and C. Xu, Journal of Membrane Science, 230, 175 (2004).

167. C. Sandoval, C. Castro, L. Gargallo, D. Radic and J. Freire, Polymer, 46, 10437 (2005).

168. A. Sarasam and S. V. Madihally, Biomaterials, 26, 5500 (2005).

169. P. Kuo, D. Sahu and H. Yu, Polymer Degradation and Stability, 91, 3097 (2006).

170. T. Caykara, A. Alaslan, M. S. Erog˘lu and O. Güven, Applied Surface Science, 252, 7430 (2006).

171. M. Mucha, J. Piekielna and A. Wieczorek, Macromolecular Symposium, 144, 391 (1999).

172. C. G. L. Khoo, S. Frantizich, A. Rosinski, M. Sjostrom and J. Hoogstraate, European Journal of Pharmaceutics and Biopharmaceutics, 55, 47 (2003).

173. T. H. M. Abou-Aiad, K. N. Abd-El-nour, I. K. Hakim and M. Z. Elsabee, Polymer, 47, 379 (2006).

174. C. H. Chen, F. Y. Wang, C. F. Mao, W. T. Liao and C. D. Hsieh, International Journal of Biological Macromolecules, 43, 37 (2008).

175. S. Tripathi, G. K. Mehrotra and P. K. Dutta, Carbohydrate Polymers, 79, 711 (2010).

176. D. Thacharodi and K. P. Rao, International Journal of Pharmaceutics, 120, 115 (1995).

177. D. Thacharodi and K. P. Rao, International Journal of Pharmaceutics, 134, 239 (1996).

178. S. Hirano, M. Zhang, M. Nakagawa, T. Miyata, Biomaterials, 21, 997 (2000).

179. M. N. Taravel and A. Domard, Biomaterials, 14, 930 (1993).

180. A. A. Salome Machado, V. C. A. Martins and A. M. G. Plepis, Journal of Thermal Analysis and Calorimetry, 67, 491 (2002).

181. S. Y. Park, B. I. Lee, S. T. Jung and H. J. Park, Materials Research Bulletin. 36. 511 (2001).

182. H. Y. Kweon, I. C. Um and Y. H. Park, Polymer, 42, 6651 (2001).

183. A. Lazaridou and C. G. Biliaderis, Carbohydrate Polymers, 48, 179 (2002).

184. M. Cheng, J. Deng, F. Yang, Y. Gong, N. Zhao and X. Zhang, Biomaterials, 24, 2871 (2003).

185. M. Zhai, L. Zhao, F. Yoshii and T. Kume, Carbohydrate Polymers, 57, 83 (2004).

186. M Mucha and A Pawlak, Thermochimica Acta, 427, 69 (2005).

187. Y. X. Xu, K. M. Kim, M A. Hanna and D. Nag, Industrial Crops and Products, 21, 185 (2005).

188. S. Wittaya-areekul and C. Prahsarn, International Journal of Pharmaceutics, 313, 123 (2006).

189. J. Yin, K. Luo, X. Chen and V. Khutoryanskiy, Carbohydrate Polymers, 63, 238 (2006).


27

190. K. C. Basavaraju, T. Damappa and S. K. Rai, Carbohydrate Polymers, 66, 357 (2006).

191. Y. Ye, W. Dan, R. Zeng, H. Lin, N. Dan, L. Guan and Z. Mi, European Polymer Journal, 43, 2066 (2007).

192. E. A. El-Hefian, M. M. Nasef, A. Yahaya and R. A. Khan, Journal of Chilean Chemical Society, 55, 130 (2010).

193. S. P. Miranda, O. Garnica, V. Sagahon and G. Cardenas, Journal of Chilean Chemical Society, 49, 173 (2004).

194. T. Thanpitcha, A. Sirivat, A. M. Jamieson and R. Rujiravanit, Carbohydrate Polymers, 64, 560 (2006).

195. C. Castro, L. Gargallo, D. Radic, G. Kortaberria and I. Mondragon, Carbohydrate Polymers, 83, 81 (2011).

196. H. M. P. Naveen Kumar, M. N. Prabhakar, C. Venkata Prasad, K. Madhusudhan Rao, T. V. Ashok Kumar Reddy, K. Chowdoji Rao and M. C. S. Subha, Carbohydrate Polymers, 82, 251 (2010).

197. T. Chandy and C. P. Sharma. Biomaterials, Artificial Cells, and Artificial Organs, 18, 1 (1990).

198. A. Berthold, K. Cremer and J. Kreuter, Journal of Controlled Release, 39, 17 (1996).

199. P. S. Adusumilli and S. M. Bolton, Drug Development and Industrial Pharmacy, 1991, 17, 1931 (1991).

200. M. Kanke, H. Katayama, S. Tsuzuki and H. Kuramoto, Chemical and Pharmaceutical Bulletin, 37, 523 (1989).

201. C. Aral and J. Akbuga, International Journal of Pharmaceutics, 168, 9 (1998).

202. J. Kristl, J. Smid-Korbar, M. Schara and H. Rupprecht, International Journal of Pharmaceutics, 99, 13 (1993).

203. L. Illum, N. F. Farraj and S. S. Davis, Pharmaceutical Research, 11, 1186 (1994).

204. C. C. Leffler and B. W. Müller, International Journal of Pharmaceutics, 194, 229 (2000).

205. H. Tozaki, J. Komoike, C. Tada, T. Maruyama, A. Terabe, T. Suzuki, A. Yamamoto

and S. Muranishi, Journal of Pharmaceutical Sciences, 86, 1016 (1997).

206. S. V. Madihally and H. W. T. Matthew, Biomaterials, 20, 1133 (1999).

207. T. W. Chung, J. Yang, T. Akaike, K. Y. Cho, J. W. Yah, S. I. Kim and C. S. Cho, Biomaterials, 23, 2827 (2002).

208. A. Gutowska, B. Jeong and M. Jasionowski, the Anatomical Record, 263, 342 (2001).

209. H. R. Ramay, Z. Li, E. Shum and M. Zhang, Journal of Biomedical Nanotechnology, 1, 151 (2005).

210. K. Kojima, Y. Okamoto, K. Miyatake, Y. Kitamura and S. Minami, Carbohydrate Polymers, 37, 109 (1998).

211. Y. Usami, Y. Okamoto, S. Minami, A. Matsuhashi, N. H Kumazawa, S. Tanioka and Y. Shigemasa, The Journal of Veterinary Medical Science, 56, 761 (1994).

212. G. A. F. Roberts, Chitin chemistr; Macmillan: London, 85 (1992).

213. M. L. Lorenzo-Lamosa, C. Remunan-Lopez, J. L. Vila-Jato and M. J. Alonso, Journal of Controlled Release, 52, 109 (1998).

214. B. Krajewska, Separation and Purification Technology, 41, 305 (2005).

215. W. Kaminski, W. Modrzejewska, Separation Science and Technology, 32, 2659 (1997).

216. S. Taha, P. Bouvet, G. Corre and G. Dorange, Advances in Chitin Science, 1, 389 (1996).

217. O. Genc, C. Arpa, G. Bayramoglu, M. Y. Arica and S. Bektas, Hydrometallurgy, 67, 53 (2002).

218. K. Koshijima, R. Tanaka, E. Muraki, Y. Akibumi and F. Yaku, Cellulose Chemistry and Technology, 7, 197 (1973).

219. B. Krajewska, Reactive and Functional Polymers, 47, 37 (2001).

220. P. Fernandez-Saiz, J. M. Lagaron, P. Hernandez-Muñoz, M J Ocio, International Journal of Food Microbiology, 124, 13 (2008).

221. S. Tripathi, G. K. Mehrotra and P. K. Dutta, International Journal of Biological Macromolecules, 45, 372 (2009).

222. S. Tripathi, G. K. Mehrotra and P. K. Dutta, Carbohydrate Polymers, 79, 711 (2010).

esam abdulkader el-hefian et al j.chem.soc.pak., …...esam abdulkader el-hefian et al.,...

Documents